2.8.2 Stereoisomerism in Glucose

Definition: Stereoisomers are molecules that have the same molecular formula but differ only in the relative arrangement of -H and -OH group in 3D space at the anomeric and asymmetric carbon atoms.

Key Terms:

• The carbon in the ring structure of monosaccharides that is derived from the carbonyl carbon of the ketone or aldehyde functional group of their open-chain form.
• Example: C-1 in glucose and ribose.

• That carbon which makes bonds with four different atoms or groups around it.
• Example: In glucose, four carbon atoms (C-2, C-3, C-4, and C-5) are asymmetric carbon atoms.

• The last asymmetric carbon atom or second last in the carbon chain.
• Example: C-5 in the case of glucose.

Number of Stereoisomers: - In monosaccharides, the number of stereoisomers depends upon the number of asymmetric carbons in its structure. - It can be calculated by the formula: 2ⁿ where n is the number of asymmetric carbon atoms. - Glucose has 4 asymmetric carbons → 2⁴ = 16 stereoisomers.

Types of Stereoisomers

Stereoisomers can be classified into the following groups:

1. Anomers

Definition: Anomers are the stereoisomers that have different positions of -H and -OH groups on the C-1 (anomeric carbon) of pentose (e.g., ribose) and hexose (e.g., glucose) and are called α or β isomers.

• If -OH group is found downward on C-1 → α sugar
• If -OH is present upward on C-1 → β sugar

Example: - α-Glucose and β-Glucose are anomers of each other.

2. Enantiomers

Definition: Those stereoisomers which are non-superimposable mirror images of one another are called enantiomers.

• Example: D (Dextro) and L (Levo) isomers of glucose.
• D isomers are also called right-handed form.
• L isomers are also called left-handed form.
• In D-glucose, the penultimate carbon (C-5) has -OH group on the right side.
• In L-glucose, the penultimate carbon has -OH group on the left side.
• Out of 16 stereoisomers of glucose, 8 are enantiomers of the other 8.

• Laboratory manufactured (artificial) sugars such as tagatose, sucralose, etc., are left-handed forms (L-sugars), and are used as sweeteners.
• Living organisms can exclusively use naturally occurring right-handed sugars (D-sugars).
• Cellular proteins, receptors, and enzymes are designed to react only with particular enantiomers (D-sugars).
• For example, the enzymes in the human stomach are right-handed and can digest only D-sugars.
• Hence, right-handed human enzymes cannot metabolize left-handed sugars because their active sites cannot fit onto a left-handed substrate.
• So, for the left-handed substrate, the enzyme must be left-handed.

3. Diastereoisomers

Definition: Those stereoisomers which have different positions of -H and -OH groups at more than one asymmetrical carbon atom are called diastereoisomers.

• Unlike enantiomers, diastereoisomers are not mirror images of each other.
• Example: D-Glucose and D-Altrose are diastereoisomers of each other.

4. Epimers

Definition: Those stereoisomers which have different arrangement of -H and -OH groups at only one asymmetrical carbon atom are called epimers.

• Example: D-Glucose and D-Mannose are epimers of each other.
• They differ at C-2 only.

Intermediate Level

Isomerism in Detail

Stereoisomerism in Detail

Key Terms:

• Formula: 2ⁿ
• n = number of asymmetric carbons
• Glucose: 4 asymmetric carbons → 2⁴ = 16 stereoisomers

Types of Stereoisomers in Detail

D and L Sugars

Why Can't Humans Metabolize L-Sugars?

• Human enzymes are stereospecific.
• They have active sites that are complementary to D-sugars.
• L-sugars have a different 3D shape.
• They cannot fit into the active sites of human enzymes.
• Therefore, L-sugars cannot be metabolized.
• They pass through the body without being broken down.
• This is why they are used as low-calorie sweeteners.

Examples of Stereoisomers of Glucose

Important Points

• 1. Isomerism: Phenomenon in which compounds have the same molecular formula but they differ in structural arrangement or formula.
• 2. Example: Glucose and fructose both are hexoses with the same molecular formula, i.e., C₆H₁₂O₆, but both have different structures of their functional groups.
• 3. Glucose is an aldo sugar and fructose is a keto sugar, so they are functional group isomers of each other.
• 4. Stereoisomerism in glucose: Stereoisomers are molecules that have the same molecular formula but differ only in the relative arrangement of -H and -OH group in 3D space at the anomeric and asymmetric carbon atoms.
• 5. Anomeric carbon is the carbon in the ring structure of monosaccharides that is derived from the carbonyl carbon of the ketone or aldehyde functional group of their open-chain form, e.g., C-1 in glucose and ribose.
• 6. Asymmetric carbon is that carbon which makes bonds with four different atoms or groups around it. For example, in glucose, four carbon atoms (C-2, C-3, C-4, and C-5) are asymmetric carbon atoms.
• 7. Last asymmetric carbon atom or second last in carbon chain (C-5 in case of glucose) is called penultimate carbon.
• 8. In monosaccharide, the number of stereoisomers actually depends upon the number of asymmetric carbons in its structure and can be calculated by the formula 2ⁿ where n is the number of asymmetric carbon atoms, so glucose has 16 stereoisomers.
• 9. Types of stereoisomers:
• - Anomers: Differ in position of -H and -OH group on C-1 (anomeric carbon) of pentose and hexose. α and β isomers.
• - Enantiomers: Non-superimposable mirror images. D and L isomers.
• - Diastereoisomers: Differ at more than one asymmetrical carbon. Not mirror images.
• - Epimers: Differ at only one asymmetrical carbon.
• 10. α and β sugars: If -OH group is found downward on C-1 → α sugar; if -OH is present upward on C-1 → β sugar.
• 11. D and L sugars: In D-glucose, penultimate carbon (C-5) has -OH group on right side; in L-glucose, penultimate carbon has -OH group on left side.
• 12. Out of 16 stereoisomers of glucose, 8 are enantiomers of the other 8.
• 13. Science Tidbits: Laboratory manufactured (artificial) sugars such as tagatose, sucralose, etc., are left-handed forms (L-sugars), and are used as sweeteners. Living organisms can exclusively use naturally occurring right-handed sugars (D-sugars). Cellular proteins, receptors, and enzymes are designed to react only with particular enantiomers (D-sugars). For example, the enzymes in human stomach are right-handed and can digest only D-sugars. Hence, right-handed human enzymes cannot metabolize left-handed sugars because their active sites cannot fit on to a left-handed substrate. So, for the left-handed substrate, the enzyme must be left-handed.

Remember

• - Isomers = same formula, different structure
• - Stereoisomers = same formula, same structural formula, different 3D arrangement
• - Glucose and Fructose = functional group isomers
• - **Anomeric carbon** = C-1
• - Asymmetric carbon = bonded to 4 different groups
• - Penultimate carbon = second last carbon (C-5 in glucose)
• - Number of stereoisomers = 2ⁿ
• - Glucose has 16 stereoisomers
• - Types of stereoisomers: Anomers, Enantiomers, Diastereoisomers, Epimers
• - **α sugar** = -OH down on C-1
• - **β sugar** = -OH up on C-1
• - D sugar = -OH on right on penultimate carbon
• - L sugar = -OH on left on penultimate carbon
• - D-sugars = natural, used by organisms
• - L-sugars = synthetic, used as sweeteners
• - 8 pairs of enantiomers among 16 stereoisomers of glucose

Common Mistakes

• 1. Confusing isomers and stereoisomers – Isomers have different structures; stereoisomers have the same structure but different 3D arrangement.
• 2. Thinking all isomers are stereoisomers – Isomers can be functional group isomers (like glucose and fructose) or stereoisomers.
• 3. Confusing anomeric and asymmetric carbon – Anomeric carbon = C-1; Asymmetric carbon = bonded to 4 different groups.
• 4. Forgetting the formula for stereoisomers – 2ⁿ where n = number of asymmetric carbons.
• 5. Confusing anomers and enantiomers – Anomers differ at C-1; Enantiomers are mirror images.
• 6. Confusing diastereoisomers and epimers – Diastereoisomers differ at more than one asymmetric carbon; Epimers differ at only one.
• 7. Thinking all sugars are D-sugars – L-sugars exist but are synthetic and used as sweeteners.
• 8. Forgetting that humans can only metabolize D-sugars – Human enzymes are right-handed and can only digest D-sugars.
• 9. Thinking L-sugars are harmful – L-sugars are not harmful; they are used as low-calorie sweeteners.
• 10. Confusing α and β sugars – α sugar = -OH down on C-1; β sugar = -OH up on C-1.
• 11. Confusing D and L sugars – D sugar = -OH on right on penultimate carbon; L sugar = -OH on left on penultimate carbon.
• 12. Thinking glucose has only one stereoisomer – Glucose has 16 stereoisomers.
• 13. Forgetting that glucose and fructose are functional group isomers – They have the same molecular formula but different functional groups.
• 14. Confusing the number of enantiomers – Out of 16 stereoisomers of glucose, 8 are enantiomers of the other 8.

Quick Revision

• Isomerism: Phenomenon in which compounds have the same molecular formula but they differ in structural arrangement or formula is called isomerism.
• For example, glucose and fructose both are hexoses with same molecular formula, i.e., C₆H₁₂O₆ but both have different structure of their functional groups.
• Glucose is an aldo sugar and fructose is a keto sugar so they are functional group isomers of each other.
• Stereoisomerism in glucose:
• Stereoisomers are molecules that have the same molecular formula but differ only in the relative arrangement of -H and -OH group in 3D space at the anomeric and asymmetric carbon atoms.
• Anomeric carbon is the carbon in the ring structure of monosaccharides that is derived from the carbonyl carbon (-6) of ketone or aldehyde functional group of their open-chain, e.g., C-1 in the glucose and ribose.
• Asymmetric carbon is that carbon which makes bonds with four different atoms or groups around it. For example, in glucose, four carbon atoms (C-2, C-3, C-4, and C-5) are asymmetric carbon atoms.
• Last asymmetric carbon atom or second last in carbon chain (C-5 in case of glucose) is called penultimate carbon.
• In monosaccharide the number of stereoisomers actually depends upon the number of asymmetric carbons in its structure and can be calculated by the formula 2ⁿ where n is the number of asymmetric carbon atoms so glucose has 16 stereoisomers.
• Stereoisomers can be classified into following groups:

60-Second Revision

• Isomers = same formula, different structure
• Stereoisomers = same formula, same structure, different 3D arrangement
• Glucose and Fructose = functional group isomers
• **Anomeric carbon** = C-1
• Asymmetric carbon = bonded to 4 different groups
• Penultimate carbon = second last carbon (C-5 in glucose)
• Number of stereoisomers = 2ⁿ
• Glucose has 16 stereoisomers
• Types: Anomers, Enantiomers, Diastereoisomers, Epimers
• **α sugar** = -OH down on C-1
• **β sugar** = -OH up on C-1
• D sugar = -OH on right on penultimate carbon
• L sugar = -OH on left on penultimate carbon
• D-sugars = natural, used by organisms
• L-sugars = synthetic, used as sweeteners
• 8 pairs of enantiomers among 16 stereoisomers of glucose
• Warning: Isomers and stereoisomers are not the same. Glucose and fructose are functional group isomers. Anomers differ at C-1; enantiomers are mirror images; epimers differ at only one asymmetric carbon. D-sugars are natural; L-sugars are synthetic. Human enzymes can only digest D-sugars. Glucose has 16 stereoisomers, not just one.